Pembrolizumab Post-IMRT for Thyroid Cancer

Overseen By Gina Tamsen

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, Pneumonitis, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, an immunotherapy, for individuals with stage IVB anaplastic thyroid carcinoma (ATC). Researchers aim to determine the effectiveness of this treatment following radiation therapy, possibly combined with chemotherapy. The goal is to assess whether pembrolizumab can extend the time patients live without cancer progression. Individuals who have undergone radiation for thyroid cancer confined to the neck and have experienced no severe side effects from previous treatments may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from promising new therapies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these, as they are part of the exclusion criteria.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab, the treatment being tested in this trial, generally has a safety profile that most people can handle without major issues. Common side effects include tiredness, muscle pain, rash, and diarrhea. More serious problems, such as thyroid issues, have also been reported, affecting thyroid function and causing symptoms like fatigue or weight changes.

Pembrolizumab is already approved for other conditions, indicating it has been found safe enough for humans in those cases. This early-phase trial aims to better understand how well patients with thyroid cancer can tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thyroid cancer?

Pembrolizumab is unique because it leverages the immune system's power to fight thyroid cancer by targeting the PD-1 pathway, which is different from traditional options like surgery and radioactive iodine. This immunotherapy is given as an infusion every six weeks, offering a potentially less invasive alternative with fewer side effects. Researchers are excited about pembrolizumab because it may provide a more effective treatment for patients who don't respond well to standard therapies, potentially improving outcomes and quality of life.

What evidence suggests that pembrolizumab might be an effective treatment for thyroid cancer?

Research has shown that pembrolizumab, which participants in this trial will receive, may be promising for treating advanced thyroid cancer. In some studies, patients with this condition had a 100% survival rate after six months of using pembrolizumab. Additionally, 58.7% of patients did not experience any worsening of their cancer during this time. Pembrolizumab has manageable side effects and has effectively shrunk tumors over time. These findings suggest that pembrolizumab could be a helpful option for patients with advanced thyroid cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Maria Cabanillas, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage IVB anaplastic thyroid cancer (ATC) who have completed radiation therapy, possibly with chemotherapy. They must be in good health overall, not pregnant or breastfeeding, and willing to use contraception. Those with certain prior treatments or immunodeficiencies, recent vaccinations, or specific genetic mutations are excluded.

Inclusion Criteria

Written informed consent for the trial

My cancer is advanced but hasn’t spread to my neck.

I am 18 or older with a diagnosis of anaplastic thyroid cancer.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I have an immune system disorder or have been on steroids or other immune-weakening drugs in the last week.

I have had previous treatments targeting my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive external beam radiation to the primary tumor, with or without concomitant chemotherapy

6-8 weeks

Treatment

Participants receive adjuvant pembrolizumab infusions every 6 weeks

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial tests pembrolizumab as an additional treatment after radiation for ATC. It aims to see how long patients can live without their cancer getting worse after this combination of therapies. Participants will receive pembrolizumab following either high-dose (>51 Gy) or lower-dose (<50 Gy) radiation.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

The infusions are given every 6 weeks

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a phase Ib trial involving 22 patients with advanced differentiated thyroid cancer, pembrolizumab showed a manageable safety profile, with 82% experiencing treatment-related adverse events, primarily diarrhea and fatigue, but no treatment-related deaths.

The treatment demonstrated limited efficacy, with an objective response rate of 9% and a median progression-free survival of 7 months, indicating that while some patients may benefit, further research is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. Mehnert, JM., Varga, A., Brose, MS., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

In a study of 103 patients with advanced thyroid cancer, pembrolizumab showed a modest objective response rate of 6.8%, with a median duration of response lasting 18.4 months, indicating some effectiveness in this challenging cancer type.

The treatment was associated with manageable toxicity, as 69.9% of patients experienced treatment-related adverse events, but only 14.6% had severe (grade 3-5) reactions, suggesting that pembrolizumab can be safely administered to this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Oh, DY., Algazi, A., Capdevila, J., et al.[2023]

Immune checkpoint inhibitors like pembrolizumab can lead to various immune-related adverse events, with thyroid dysfunction being a common issue.

This report highlights a rare case of Graves' disease causing thyrotoxicosis in a 50-year-old patient undergoing pembrolizumab therapy, emphasizing the need for awareness of this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rare Case of Pembrolizumab-Associated Graves' Disease. Alqaisi, S., Rahman, A.[2023]

Citations

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Efficacy and safety of pembrolizumab monotherapy in ... Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001641

Effectiveness of immune checkpoint inhibitor therapy in ... Most studies reported that pembrolizumab was generally well tolerated. Rates of AEs and TRAEs spanned as high as 100 % and 82 % respectively [29 ...

3. cinj.org cinj.org/fighting-advanced-thyroid-cancer-immunotherapy

Fighting Advanced Thyroid Cancer with Immunotherapy The six-month overall survival rate was 100 percent and the six month progression free survival rate was 58.7 percent. Updated results will be announced at the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10882904/

First effectiveness data of lenvatinib and pembrolizumab as ... Here, we present real-world outcome data on the activity of the combination of lenvatinib and pembrolizumab as a systemic first-line therapy ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34657

Efficacy and safety of pembrolizumab monotherapy in patients ... Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These ...

6. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf Safety data are available for the first 203 patients who received KEYTRUDA and chemotherapy (n=101) or placebo and chemotherapy (n=102). Patients with ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/125514s096lbl.pdf

Keytruda - accessdata.fda.gov Safety data are available for the first 203 patients who received KEYTRUDA and chemotherapy (n=101) or placebo and chemotherapy (n=102). Patients with ...

8. keytrudahcp.com keytrudahcp.com/safety/adverse-reactions/

Select Adverse Reactions for KEYTRUDA® (pembrolizumab) KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism.

9. keytruda.com keytruda.com/side-effects/

Side Effects of KEYTRUDA® (pembrolizumab) Common side effects of KEYTRUDA when used alone include: feeling tired, pain, including pain in muscles, rash, diarrhea, fever, cough, decreased appetite, ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30832606/

Safety and antitumor activity of the anti-PD-1 ... - PubMed Results of this phase Ib proof-of-concept study suggest that pembrolizumab has a manageable safety profile and demonstrate evidence of antitumor activity.